Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study.

Seronegative celiac disease (CD) poses a diagnostic challenge. Characterize and identify differences between seronegative and seropositive CD. Retrospective cohort study examining adult patients diagnosed with CD (1980-2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression. Of 315 CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% 9.7%,  = .016), HLA-DQ8 heterozygosity (23.1% 2.5%,  ˂ .001) and Marsh I lesion (34.6% 3.7%,  ˂ .001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD. Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.